Seasonal evolution of Titan's stratosphere during the Cassini mission.

Titan's stratosphere exhibits significant seasonal changes, including break-up and formation of polar vortices. Here we present the first analysis of mid-infrared mapping observations from Cassini's Composite InfraRed Spectrometer (CIRS) to cover the entire mission (Ls=293-93°, 2004-2017) - mid-northern winter to northern summer solstice. The north-polar winter vortex persisted well after equinox, starting break-up around Ls∼60°, and fully dissipating by Ls∼90°. Absence of enriched polar air spreading to lower latitudes suggests large-scale circulation changes and photochemistry control chemical evolution during vortex break-up. South-polar vortex formation commenced soon after equinox and by Ls∼60° was more enriched in trace gases than the northern mid-winter vortex and had temperatures ∼20 K colder. This suggests early-winter and mid-winter vortices are dominated by different processes - radiative cooling and subsidence-induced adiabatic heating respectively. By the end of the mission (Ls=93°) south-polar conditions were approaching those observed in the north at Ls=293°, implying seasonal symmetry in Titan's vortices.

Retinal detachment repair and cataract surgery in patients with atopic dermatitis.

PurposeThe aim of this study is to report a case series of ocular complications including retinal detachment (RD) and cataract in atopic dermatitis (AD) and surgical management involving a majority of Caucasian patients.Patients and methodsThis study is an observational case series, originally designed as an audit. It involves detailed discussion of history, clinical features, and surgical management of patients presenting with retinal detachment and cataracts secondary to severe AD. Six consecutive patients with diagnosis of severe AD requiring posterior segment and cataract surgery were included in the study.ResultsEight eyes of six patients had retinal detachment. Most of them involved the temporal retina. The retinal breaks were located anteriorly close to the ora serrata in six eyes and Giant tear retinal (GRT) detachment was found in two eyes. Five eyes had proliferative vitreo-retinopathy (PVR) at presentation. All six patients had bilateral cataracts and cataract surgery was performed in eleven eyes. Bilateral simultaneous surgery was essential in two patients. Three eyes had secondary intra-ocular lens (IOL) implantation with pars plana vitrectomy for subluxed lens implant.ConclusionsAnterior retinal breaks and temporal RD are common in retinal detachment secondary to AD. PVR is often present, which makes surgical management difficult. Cataract formation is quite often and late subluxation of IOL may occur.

Comprehensive microRNA profiling in acetaminophen toxicity identifies novel circulating biomarkers for human liver and kidney injury.

Our objective was to identify microRNA (miRNA) biomarkers of drug-induced liver and kidney injury by profiling the circulating miRNome in patients with acetaminophen overdose. Plasma miRNAs were quantified in age- and sex-matched overdose patients with (N = 27) and without (N = 27) organ injury (APAP-TOX and APAP-no TOX, respectively). Classifier miRNAs were tested in a separate cohort (N = 81). miRNA specificity was determined in non-acetaminophen liver injury and murine models. Sensitivity was tested by stratification of patients at hospital presentation (N = 67). From 1809 miRNAs, 75 were 3-fold or more increased and 46 were 3-fold or more decreased with APAP-TOX. A 16 miRNA classifier model accurately diagnosed APAP-TOX in the test cohort. In humans, the miRNAs with the largest increase (miR-122-5p, miR-885-5p, miR-151a-3p) and the highest rank in the classifier model (miR-382-5p) accurately reported non-acetaminophen liver injury and were unaffected by kidney injury. miR-122-5p was more sensitive than ALT for reporting liver injury at hospital presentation, especially combined with miR-483-3p. A miRNA panel was associated with human kidney dysfunction. In mice, miR-122-5p, miR-151a-3p and miR-382-5p specifically reported APAP toxicity - being unaffected by drug-induced kidney injury. Profiling of acetaminophen toxicity identified multiple miRNAs that report acute liver injury and potential biomarkers of drug-induced kidney injury.

Engineering nanostructures by binding single molecules to single-walled carbon nanotubes.

Organic and hybrid organic-inorganic systems are promising candidates for low cost photovoltaics. Recently, perovskite-based systems have been attracting a large amount of research attention, where the highest performing devices employ a small molecule (2,2',7,7'-tetrakis(N,N-di-p-methoxyphenyl-amine)-9,9'-spirobifluorene) (Spiro-OMeTAD) hole transporter. Here, we demonstrate the production of single-walled carbon nanotube (SWNT)/single molecule nanostructures using a simple solution processing technique for effective and strong binding of Spiro-OMeTAD to individual polymer-wrapped SWNTs. These small molecules bind very strongly, which causes both large mechanical strain of the nanotubes and also improves the separation of individual SWNTs, thus improving the nanotube photoluminescence quantum efficiency by 1 order of magnitude compared to simple polymer-nanotube nanohybrids. Using absorption and photoluminescence measurements, we show that there is a dramatic variation in the electronic properties of the polymer-NT nanocomposites due to the band alignment formed with Spiro-OMeTAD. These self-assembled nanocomposites offer the potential for integration into high performance optoelectronic such as photovoltaic cells and light emission devices.

Physical limitations in meal preparation and consumption are associated with lower musculoskeletal nutrient (calcium, vitamin D, magnesium, and phosphorus) intakes in homebound older adults.

OBJECTIVES: Although homebound older adults are at increased risk for poor nutritional health and adverse nutrition-related outcomes, little attention has focused on the tasks involved in meal preparation and consumption and the influence of those tasks on dietary intake. METHODS: We examined the self-reported dietary intake from 3, 24-h dietary recalls and physical limitations in meal preparation and consumption (LMPC) activities from a randomly recruited sample of 345 homebound older men and women. Ordered logistic regression was used to examine the correlation of demographic characteristics and 6 activities with relative intakes of key musculoskeletal nutrients (calcium, vitamin D, magnesium, and phosphorus). RESULTS: At least 70% reported not meeting ⅔ recommended intakes for calcium and vitamin D; 12.5% failed to achieve ⅔ recommended intakes in at least three of the four nutrients. More than 12% of the sample reported it was very difficult or they were unable to perform at least 3 LMPC tasks. Regression results indicated that reporting the greatest LMPC increased the odds for lower intake of musculoskeletal nutrients. CONCLUSION: Independent of sociodemographic characteristics, self-reported difficulty in meal preparation and consumption was associated with lower dietary intakes of musculoskeletal nutrients. These results suggest the need to assess difficulty in meal preparation and consumption for the growing population of homebound older adults who participate in supplemental nutrition programs. This brief, 6-item measure may help identify older adults at risk of poor nutritional health and declining function.

Putative TRP channel antagonists, SKF 96365, flufenamic acid and 2-APB, are non-competitive antagonists at recombinant human α1ß2γ2 GABA(A) receptors.

Although transient receptor potential (TRP) channel biology research has expanded rapidly in recent years, the field is hampered by the widely held, but relatively poorly investigated, belief that most of the pharmacological tools used to investigate TRP channel function may not be particularly selective for their intended targets. The objective of this study was therefore to determine if this was indeed the case by systematically evaluating the effects of three routinely used putative TRP channel antagonists, SKF 96365, flufenamic acid (FF) and 2-aminoethoxydiphenyl borate (2-APB) against one of the most widely expressed CNS receptor subtypes CNS, the human α1ß2γ2 GABA(A) receptor. Using whole cell patch-clamp recording to record responses to rapidly applied GABA in the absence and presence of the three putative antagonists in turn we found that SKF 96365 (1-100 µM) and FF (1-100 µM) significantly inhibited GABA responses of recombinant human α1ß2γ2 GABA(A) receptor stably expressed in HEK293 cells with IC(50) values of 13.4 ± 5.1 and 1.9 ± 1.4 µM, respectively, suppressing the maximal response to GABA at all concentrations used in a manner consistent with a non-competitive mode of action. SKF 96365 and FF also both significantly reduced desensitisation and prolonged the deactivation kinetics of the receptors to GABA (1mM; P<0.05). 2-APB (10-1000 µM) also inhibited responses to GABA at all concentrations used with an IC(50) value of 16.7 ± 5.4 µM (n=3-5) but had no significant effect on the activation, desensitisation or deactivation kinetics of the GABA responses. Taken together this investigation revealed that these widely utilised TRP channel antagonists display significant 'off-target' effects at concentrations that are routinely used for the study of TRP channel function in numerous biological systems and as such, data which is obtained utilising these compounds should be interpreted with caution.

A British Ophthalmological Surveillance Unit study on serious ocular injuries from fireworks in the UK.

PURPOSE: We conducted a surveillance study to assess the nature, management, and visual outcomes of serious ocular injuries from fireworks in the UK. METHODS: New cases of serious ocular injuries from fireworks were prospectively ascertained through the monthly active surveillance system of the British Ophthalmological Surveillance Unit (BOSU). All ophthalmologists in the UK received a reporting card each month for a 2-year period commencing July 2004. They were asked to indicate any new cases of serious ocular injury from a firework, or to confirm that they had no new cases to report. Information on demographic detail, type of injury, management, and visual outcome was sought through an incident and 6-month follow-up questionnaire. RESULTS: Eighty-one per cent of the injuries occurred in October and November and 27% (13/47) of the patients were less than 18 years old. Twenty-six per cent (12/47) of patients had a penetrating injury, and ocular surgery was required in 53% (25/47) of cases. Eight patients (17%) required enucleation or evisceration and four (9%) required a cosmetic shell for phthisis. At 6-month follow-up, 53% (21/40) of cases had a visual acuity of 6/60 or worse. CONCLUSION: This prospective national survey confirms that firework injuries are an important cause of preventable visual disability particularly to young males. It is likely that such injuries occur year on year and as such represent an important public health concern in addition to the burden placed upon the health service.

Association of resident, facility, and geographic characteristics with chronic undernutrition in a nationally represented sample of older residents in U.S. nursing homes.

BACKGROUND: Undernutrition (also known as protein-calorie malnutrition or energy-deficiency) is associated with exacerbation of health conditions, increased frailty, and decline in physical, cognitive, and affective function. This is a critical problem for older adults who reside in nursing homes and have many limitations that contribute to reduced food intake. OBJECTIVE: To determine the relationship of chronic undernutrition [body mass index (BMI) < 18.5 kg/m2] to resident, facility, and geographical characteristics in a national sample of nursing home residents aged 60 y or older in the U.S. DESIGN: A cross-sectional, secondary analysis of a 10% nationally representative random sample of annual assessments of nursing home residents in the U.S. (n = 128,514), using the Minimum Data Set (MDS). Data included measured weight and height, resident characteristics, facility characteristics, and geographic location. RESULTS: More than 12% (n = 15,566) were chronically undernourished (energy-deficient), with more than 27% of those being severely undernourished (BMI < 16). Independent correlates of chronic undernutrition (multivariate analysis) included resident characteristics (ADL, having chewing or swallowing problems, or leaving at least 25% of the meal uneaten), facility characteristics (% Medicare and for-profit status), and geographic characteristics (living in nursing home in urban or large towns). CONCLUSION: This study found a high percentage of chronic undernutrition in this nationally representative sample of U.S. nursing home residents. Furthermore, resident, facility, and geographic characteristics were associated with chronic undernutrition. Strategies need to be developed and documented that ensure nutritional health to residents with a variety of health problems.

Nucleophosmin is a novel Bax chaperone that regulates apoptotic cell death.

The proapoptotic B-cell lymphoma-2 family protein Bax is a key regulatory point in the intrinsic apoptotic pathway. However, the factors controlling the process of Bax activation and translocation to mitochondria have yet to be fully identified and characterized. We performed affinity chromatography using peptides corresponding to the mitochondrial-targeting region of Bax, which is normally sequestered within the inactive structure. The molecular chaperone nucleophosmin was identified as a novel Bax-binding protein by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Reciprocal co-immunoprecipitation and proximity assays confirmed the Bax-nucleophosmin protein-protein interaction and verified that nucleophosmin only bound to activated conformationally altered Bax. Confocal microscopy in a cell-based apoptosis model, demonstrated that nucleophosmin translocation from nucleolus to cytosol preceded Bax movement. Specific knockdown of nucleophosmin expression using RNAi attenuated apoptosis as measured by mitochondrial cytochrome c release and activation of the caspase cascade. In a mouse model of ischaemic stroke, subcellular fractionation studies verified that nucleophosmin translocation occurred within 3 h, at a time before Bax translocation but after Bax conformational changes have occurred. Thus, we have elucidated a novel molecular mechanism whereby Bax becomes activated and translocates to the mitochondria to orchestrate mitochondrial dysfunction and apoptotic cell death, which opens new avenues for therapeutic intervention.

Differential regulation of caspase-3 by pharmacological and developmental stimuli as demonstrated using humanised caspase-3 mice.

Caspase-3 is a potential therapeutic target for a number of degenerative diseases. However the development of specific caspase-3 inhibitors has been hampered by inter-species differences and the high degree of homology shared by different caspases. To circumvent these issues, we have produced and characterised a humanised caspase-3 mouse line (possessing one copy of the human gene with both copies of the murine gene disrupted) by crossing human caspase-3 transgenic mice with nullizygous caspase-3 knock-out mice. Humanised mice appeared normal and survived to adulthood. Analysis of the human gene revealed that human pro-caspase-3 was expressed in the same tissues as its murine counterpart. However humanised mice retained the hypercellularity of frontal cortex seen in their knock-out parental line and there was no biochemical evidence of human protein processing during naturally occurring neuronal death taking place during brain development. In contrast, the human protein was cleaved by the mouse machinery following anti-Fas treatment of adult mice. These data suggest that there is a fundamental difference between the activation pathways leading to caspase-3 cleavage during naturally occurring cell death in development/embryogenesis and following an apoptotic stimulus in the adult.

Nutrient intake and BMI as predictors of severity of ADL disability over 1 year in homebound elders.

PURPOSE: Although it is well-recognized that good nutrition is essential to health, quality of life, and disease management, evidence of the role of nutrition, especially dietary intake, in the development of health-related disability among the more vulnerable older men and women in the community is largely unavailable. METHODS: We examined self-reported and performance-based measures at baseline (demographic, psychosocial and health-related factors, BMI, burden of disease, dietary intake from 3 24-hour dietary recalls, lower extremity physical performance, and activities of daily living [ADL]) and 1-year follow-up (ADL) from a randomly recruited sample of homebound elders. Structural equation modeling was used to simultaneously evaluate the direct and indirect relationships among baseline factors and severity of disability in activities of daily living (ADL) at 1-year in 253 homebound elders. results: Almost 32% of the homebound sample reported increased severity of disability over 1 year. The full structural model fit the data very well and revealed that better summary intake of calcium, vitamin D, magnesium, and phosphorus was directly linked to better lower extremity performance (LEP) and indirectly to less severity of disability at one year, after controlling for baseline disability and the interrelationships of other factors. Greater BMI was directly associated with worse LEP and indirectly with greater severity of disability. CONCLUSIONS: The findings from this study acknowledge aspects of the complex direct and indirect relationships between nutrient intake, BMI, and disability among homebound elders. These results suggest that nutrient intake and BMI may be reasonable targets for intervention with multiple functional outcomes.

Mice overexpressing human caspase 3 appear phenotypically normal but exhibit increased apoptosis and larger lesion volumes in response to transient focal cerebral ischaemia.

Caspase 3 activation has been implicated in cell death following a number of neurodegenerative insults. To determine whether caspase genes can affect the susceptibility of cells to neurodegeneration, a transgenic mouse line was created, expressing human caspase 3 under control of its own promoter. The human gene was regulated by the murine homeostatic machinery and human procaspase 3 was expressed in the same tissues as mouse caspase 3. These novel transgenic mice appeared phenotypically and developmentally normal and survived in excess of 2 years. Behavioural assessment using the 5-choice serial reaction time task found no differences from wild-type littermates. Caspase activity was found to be tightly regulated under physiological conditions, however, significantly larger lesions were obtained when transgenic mice were subjected to focal cerebral ischaemia/reperfusion injury compared to wild-type littermates. These data demonstrate that mice overexpressing human caspase 3 are essentially normal, however, they have increased susceptibility to degenerative insults.

Management of endophthalmitis with retained intraocular foreign body.

AIMS: To assess the impact of primary injection of intravitreal antibiotics and delayed pars plana vitrectomy with removal of intraocular foreign body (IOFB) in patients with clinical features of bacterial endophthalmitis and retained IOFB. METHODS: Retrospective review of all patients with clinical features of infective endophthalmitis and a retained IOFB who had immediate injection of intravitreal antibiotics and delayed pars plana vitrectomy with removal of IOFB in two vitreo-retinal centres during 1995-2001. Nine patients were identified and minimum follow-up was 3 months. RESULTS: Four of the nine patients had a final visual outcome of 6/18 or better. One patient developed total retinal detachment. CONCLUSIONS: The current series suggests that immediate injection of intravitreal antibiotics with delayed removal of IOFB in eyes with clinical features of infective endophthalmitis and a retained IOFB is a possible alternative to immediate removal of IOFB. This management may be associated with preservation of the eye and restoration of useful visual acuity.

Serious eye and adnexal injuries from fireworks in Northern Ireland before and after lifting of the firework ban--an ophthalmology unit's experience.

BACKGROUND/AIMS: To report serious fireworks-related eye and adnexal injuries presenting to the Department of Ophthalmology in the Royal Victoria Hospital, Belfast. To assess the effect of lifting of the legislative ban on fireworks in Northern Ireland in 1996. METHOD: Twelve year retrospective review from 1990 to 2001 inclusive of all ocular and adnexal injuries from fireworks requiring hospitalisation to the ophthalmology department. RESULTS: Twenty three patients with 23 injured eyes were reported. Six were female. The mean age was 18 years (+/- 13 SD). Six patients presented between the years 1990 and 1995. The remaining 17 patients presented between 1996 and 2001. Nearly half of the patients required ophthalmic surgical procedures. Thirty-six percent of patients had a final visual acuity of 6/60 or less. Superficial trauma not requiring hospitalisation was not included. CONCLUSION: Removal of the legislative ban on fireworks in 1996 has had a significant effect on the incidence of eye injuries. These injuries are potentially preventable with stricter control on the availability of fireworks and a greater awareness of the ocular risks they pose.

[3H]dofetilide binding to HERG transfected membranes: a potential high throughput preclinical screen.

The pharmacological characteristics of [3H]dofetilide binding were examined in membranes prepared from human embryonic kidney (HEK293) cells stably expressing human ether-á-go-go related gene (HERG) K+ channels. The classIII antiarrhythmic compounds dofetilide, clofilium, 4'-[[1-[2-(6-methyl-2-pyridyl)ethyl]-4-piperidyl]carbonyl]methanesulfonanilide (E-4031), N-methyl-N-[2-[methyl-(1-methyl-1H-benzimidazol-2-yl)amino]ethyl]-4-[(methylsulfonyl)amino]benzene-sulfonamide (WAY-123,398) and d-sotalol all inhibited [3H]dofetilide binding. In addition, the structurally unrelated compounds pimozide, terfenadine and haloperidol, all of which prolong the QT interval in man, also inhibited binding. These data indicate that a [3H]dofetilide binding assay using HERG membranes may help identify compounds that prolong the QT interval.

The feasibility of using a telephone-administered survey for determining nutritional service needs of noninstitutionalized older adults in rural areas: time and costs.

PURPOSE: This study examined response, participation, time, and costs for a telephone-administered survey to obtain comprehensive information on general health, eating habits, living environment, and functional status from a sample of older persons in a rural North Carolina county. DESIGN AND METHODS: A probability sample of persons aged 60 years and older from the most recent electoral rolls were mailed a personalized letter, which was followed by telephone contact to recruit them into a contemporaneous survey that used a modified version of the Nutrition Screening Initiative's Level I and II screens. Time requirements and costs associated with the completion of surveys were calculated. RESULTS: Seventy-six percent of the persons contacted by telephone (residents of 96% of county precincts) completed the survey. Because minority elders were more likely to lack a working telephone, they were underrepresented in the sample. With 555 calling attempts (58% of surveys completed on first attempt), we estimated a cost of $10.65 per completed survey. IMPLICATIONS: Telephone-administered surveying of older adults may be considered as an appropriate component of an overall community-based service strategy. The estimation of the constituents of nutritional risk, by geographic area, economic status, or ethnicity, may aid in providing estimates of service needs and procuring and allocating resources. Additional methods of data collection are necessary in order to target older persons without telephone service.